Liver HFE protein content is posttranscriptionally decreased in iron-deficient mice and rats

0503582 - BTÚ 2019 RIV US eng J - Článek v odborném periodiku
Frýdlová, J. - Rogalsky, D.W. - Truksa, Jaroslav - Traeger, L. - Steinbicker, A. U. - Vokurka, M. - Krijt, J.
Liver HFE protein content is posttranscriptionally decreased in iron-deficient mice and rats.
American Journal of Physiology-Gastrointestinal and Liver Physiology. Roč. 315, č. 4 (2018), G560-G568. ISSN 0193-1857. E-ISSN 1522-1547
Grant CEP: GA ČR GA13-28830S
Institucionální podpora: RVO:86652036
Klíčová slova: ALK3 * hemojuvelin * hepcidin * matriptase-2
Obor OECD: Gastroenterology and hepatology
Impakt faktor: 3.729, rok: 2018

Although the relationship between hereditary hemochromatosis and mutations in the HFE gene was discovered more than 20 years ago, information on the in vivo regulation of HFE protein expression is still limited. The purpose of the study was to determine the response of liver HFE protein content to iron deficiency in mice and rats by immunoblotting. Attempts to visualize the HFE protein in whole liver homogenates were unsuccessful, however, HFE could be detected in liver microsomes or in plasma membrane-enriched fractions. Five-week-old male C57BL/6 mice fed an iron-deficient diet for 4 wk presented with a significant decrease in liver iron content and liver Hamp expression, as well as with a significant decrease in liver HFE protein content. Rats fed an iron-deficient diet for 4 wk also displayed significant decrease in liver Hamp expression and liver HFE protein content. These results suggest that the downregulation of HFE-dependent signaling may contribute to decreased Hamp gene expression in states of prolonged iron deficiency. It has recently been proposed that HFE protein could be a potential target of matriptase-2, a hepatocyte protease mutated in iron-refractory iron deficiency anemia. However, immunoblot analysis of HFE protein in the livers from Tmprss6-mutated mask mice did not show evidence of matriptase-2-dependent HFE protein cleavage. In addition, no indication of HFE protein cleavage was seen in iron-deficient rats, whereas the full-length matriptase-2 protein content in the same animals was significantly increased. These results suggest that HFE is probably not a major physiological target of matriptase-2.
Trvalý link: http://hdl.handle.net/11104/0295395